MARK2_MOUSE
ID MARK2_MOUSE Reviewed; 776 AA.
AC Q05512; Q3T9L3; Q6PDR4; Q8BR95;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Serine/threonine-protein kinase MARK2;
DE EC=2.7.11.1;
DE EC=2.7.11.26;
DE AltName: Full=ELKL motif kinase 1;
DE Short=EMK-1;
DE AltName: Full=MAP/microtubule affinity-regulating kinase 2;
DE AltName: Full=PAR1 homolog;
DE AltName: Full=PAR1 homolog b;
DE Short=Par-1b;
DE Short=mPar-1b;
GN Name=Mark2; Synonyms=Emk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Embryo;
RX PubMed=8358177; DOI=10.1007/bf00360595;
RA Inglis J.D., Lee M., Hill R.E.;
RT "Emk, a protein kinase with homologs in yeast maps to mouse chromosome
RT 19.";
RL Mamm. Genome 4:401-403(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=129; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10491259; DOI=10.1006/dbio.1999.9379;
RA Bessone S., Vidal F., Le Bouc Y., Epelbaum J., Bluet-Pajot M.T., Darmon M.;
RT "EMK protein kinase-null mice: dwarfism and hypofertility associated with
RT alterations in the somatotrope and prolactin pathways.";
RL Dev. Biol. 214:87-101(1999).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=11287624; DOI=10.1128/mcb.21.9.3206-3219.2001;
RA Hurov J.B., Stappenbeck T.S., Zmasek C.M., White L.S., Ranganath S.H.,
RA Russell J.H., Chan A.C., Murphy K.M., Piwnica-Worms H.;
RT "Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-
RT 1) protein kinase.";
RL Mol. Cell. Biol. 21:3206-3219(2001).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=17372192; DOI=10.1073/pnas.0701179104;
RA Hurov J.B., Huang M., White L.S., Lennerz J., Choi C.S., Cho Y.R.,
RA Kim H.J., Prior J.L., Piwnica-Worms D., Cantley L.C., Kim J.K.,
RA Shulman G.I., Piwnica-Worms H.;
RT "Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic
RT rate, decreased adiposity, and insulin hypersensitivity in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5680-5685(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453; SER-483 AND SER-568, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Serine/threonine-protein kinase. Involved in cell polarity
CC and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX,
CC HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the
CC microtubule-associated protein MAPT/TAU. Plays a key role in cell
CC polarity by phosphorylating the microtubule-associated proteins MAP2,
CC MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules,
CC and their disassembly. Regulates epithelial cell polarity by
CC phosphorylating RAB11FIP2. Involved in the regulation of neuronal
CC migration through its dual activities in regulating cellular polarity
CC and microtubule dynamics, possibly by phosphorylating and regulating
CC DCX. Regulates axogenesis by phosphorylating KIF13B, promoting
CC interaction between KIF13B and 14-3-3 and inhibiting microtubule-
CC dependent accumulation of KIF13B. Also required for neurite outgrowth
CC and establishment of neuronal polarity. Regulates localization and
CC activity of some histone deacetylases by mediating phosphorylation of
CC HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and
CC export from the nucleus. Also acts as a positive regulator of the Wnt
CC signaling pathway, probably by mediating phosphorylation of dishevelled
CC proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision
CC to build a columnar versus a hepatic epithelial cell apparently by
CC promoting a switch from a direct to a transcytotic mode of apical
CC protein delivery. Essential for the asymmetric development of membrane
CC domains of polarized epithelial cells. {ECO:0000250|UniProtKB:Q7KZI7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by PAK5; inhibition is independent of
CC the kinase activity of PAK5. Activated by phosphorylation on Thr-208.
CC Inhibited by phosphorylation at Ser-212 and Thr-593. Inhibited by
CC hymenialdisine (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with PAK5; leading to inhibit the protein
CC kinase activity (By similarity). Interacts with MAPT/TAU. Interacts
CC with MTCL1; the interaction is direct and increases MARK2 microtubule-
CC binding ability. Interacts (when phosphorylated at Thr-593) with YWHAZ
CC (By similarity). Interacts with YWHAB, YWHAG and YWHAQ (By similarity).
CC {ECO:0000250|UniProtKB:O08679, ECO:0000250|UniProtKB:Q7KZI7}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Lateral cell membrane {ECO:0000250}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q7KZI7}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q7KZI7}. Note=Phosphorylation at Thr-593 by
CC PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ
CC promotes relocation from the cell membrane to the cytoplasm.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q05512-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q05512-2; Sequence=VSP_013341;
CC Name=3;
CC IsoId=Q05512-3; Sequence=VSP_013342;
CC Name=4;
CC IsoId=Q05512-4; Sequence=VSP_013342, VSP_022597;
CC -!- TISSUE SPECIFICITY: Highly expressed in adult kidney and testis, lower
CC levels in heart, brain, spleen, lung and liver. Expressed in the head
CC and neural fold in 8 dpc embryos, the limb buds, telencephalic
CC vesicles, eyes, branchial archs and heart at 11.5 dpc, the ectoderm at
CC 13 dpc and epiderm, hair and whisker follicles at 15 dpc.
CC {ECO:0000269|PubMed:10491259}.
CC -!- DOMAIN: The UBA domain does not seem to bind ubiquitin and ubiquitin-
CC like and might play a role in regulating the enzyme conformation and
CC localization. Activation of the kinase activity following
CC phosphorylation at Thr-208 is accompanied by a conformational change
CC that alters the orientation of the UBA domain with respect to the
CC catalytic domain (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The KA1 domain mediates binding to phospholipids and targeting
CC to membranes. {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in
CC complex with STE20-related adapter-alpha (STRADA) pseudo kinase and
CC CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase
CC activity, leading to phosphorylation and detachment of MAPT/TAU from
CC microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits
CC the kinase activity. Phosphorylation by CaMK1 promotes activity and is
CC required to promote neurite outgrowth. Phosphorylation at Thr-593 by
CC PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity
CC and promotes binding to 14-3-3 protein YWHAZ, leading to relocation
CC from cell membrane to cytoplasm (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice have no embryonic defect and are viable.
CC They do not display obvious neuronal phenotype, possibly due to genetic
CC redundancy with Mark1, Mark3 and Mark4. They however show an overall
CC proportionate dwarfism and a peculiar hypofertility: homozygotes are
CC not fertile when intercrossed, but are fertile in other types of
CC crosses. They also show immune-cell dysfunction. As mice age, they
CC develop splenomegaly, lymphadenopathy, membranoproliferative
CC glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid
CC glands and kidneys. Moreover, mice are lean, insulin hypersensitive,
CC resistant to high-fat-diet-induced weight gain, and hypermetabolic.
CC {ECO:0000269|PubMed:10491259, ECO:0000269|PubMed:11287624,
CC ECO:0000269|PubMed:17372192}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC32312.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X70764; CAA50040.1; -; mRNA.
DR EMBL; AK045329; BAC32312.1; ALT_FRAME; mRNA.
DR EMBL; AK172444; BAE43007.1; -; mRNA.
DR EMBL; BC058556; AAH58556.1; -; mRNA.
DR CCDS; CCDS37903.1; -. [Q05512-4]
DR CCDS; CCDS37904.1; -. [Q05512-1]
DR CCDS; CCDS50378.1; -. [Q05512-3]
DR PIR; I48609; I48609.
DR RefSeq; NP_001073857.1; NM_001080388.2.
DR RefSeq; NP_001073858.1; NM_001080389.2.
DR RefSeq; NP_001073859.1; NM_001080390.2.
DR RefSeq; NP_031954.2; NM_007928.3.
DR AlphaFoldDB; Q05512; -.
DR SMR; Q05512; -.
DR BioGRID; 199437; 31.
DR IntAct; Q05512; 15.
DR MINT; Q05512; -.
DR STRING; 10090.ENSMUSP00000131684; -.
DR iPTMnet; Q05512; -.
DR PhosphoSitePlus; Q05512; -.
DR EPD; Q05512; -.
DR jPOST; Q05512; -.
DR MaxQB; Q05512; -.
DR PaxDb; Q05512; -.
DR PeptideAtlas; Q05512; -.
DR PRIDE; Q05512; -.
DR ProteomicsDB; 295830; -. [Q05512-1]
DR ProteomicsDB; 295831; -. [Q05512-2]
DR ProteomicsDB; 295832; -. [Q05512-3]
DR ProteomicsDB; 295833; -. [Q05512-4]
DR DNASU; 13728; -.
DR GeneID; 13728; -.
DR KEGG; mmu:13728; -.
DR UCSC; uc008gks.2; mouse. [Q05512-4]
DR UCSC; uc008gkt.2; mouse. [Q05512-3]
DR CTD; 2011; -.
DR MGI; MGI:99638; Mark2.
DR eggNOG; KOG0586; Eukaryota.
DR InParanoid; Q05512; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q05512; -.
DR BioGRID-ORCS; 13728; 9 hits in 76 CRISPR screens.
DR ChiTaRS; Mark2; mouse.
DR PRO; PR:Q05512; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q05512; protein.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0045180; C:basal cortex; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0097427; C:microtubule bundle; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; ISO:MGI.
DR GO; GO:0050321; F:tau-protein kinase activity; ISS:UniProtKB.
DR GO; GO:0061564; P:axon development; ISO:MGI.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0071963; P:establishment or maintenance of cell polarity regulating cell shape; ISO:MGI.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; ISS:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:1904526; P:regulation of microtubule binding; ISO:MGI.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISO:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00627; UBA; 1.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50032; KA1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Cytoplasm; Cytoskeleton; Developmental protein; Differentiation; Kinase;
KW Lipid-binding; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..776
FT /note="Serine/threonine-protein kinase MARK2"
FT /id="PRO_0000086302"
FT DOMAIN 53..304
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 323..362
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 727..776
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..429
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..444
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 175
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 59..67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 58
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 91
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 92
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 93
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 208
FT /note="Phosphothreonine; by LKB1 and TAOK1"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 212
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 274
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 275
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 294
FT /note="Phosphothreonine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08679"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 464
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 566
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 593
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 616
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 710
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT VAR_SEQ 321..339
FT /note="PDYKDPRRTELMVSMGYTR -> LTTGPRDRVDGVNGLHT (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:8358177"
FT /id="VSP_013341"
FT VAR_SEQ 502..555
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_013342"
FT VAR_SEQ 640
FT /note="V -> VRRNLSFRFA (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022597"
FT CONFLICT 161..162
FT /note="SA -> LH (in Ref. 1; CAA50040)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="L -> P (in Ref. 1; CAA50040)"
FT /evidence="ECO:0000305"
FT CONFLICT 760
FT /note="S -> Y (in Ref. 2; BAC32312)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 776 AA; 86306 MW; 533C8DE0B5EC507E CRC64;
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMLRGRNS ATSADEQPHI GNYRLLKTIG
KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE
TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN
LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKIDGPE VDVWSLGVIL
YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK
DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL
LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRSSD QAVPAIPTSN
SYSKKTQSNN AENKRPEEET GRKASSTAKV PASPLPGLDR KKTTPAPSTN SVLSTSTNRS
RNSPLLDRAS LGQASIQNGK DSLTMPGSRA STASASAAVS AARPRQHQKS MSASVHPNKA
SGLPPTESNC EVPRPSTAPQ RVPVASPSAH NISSSSGAPD RTNFPRGVSS RSTFHAGQLR
QVRDQQNLPY GVTPASPSGH SQGRRGASGS IFSKFTSKFV RRNLNEPESK DRVETLRPHV
VGSGGTDKDK EEFREAKPRS LRFTWSMKTT SSMEPNEMMR EIRKVLDANS CQSELHERYM
LLCVHGTPGH ENFVQWEMEV CKLPRLSLNG VRFKRISGTS MAFKNIASKI ANELKL
